Laterally Spreading Type of Colorectal Adenoma Exhibits a Unique Methylation Phenotype and K-ras Mutations

Sakiko Hiraoka, Jun Kato, Masashi Tatsukawa, Keita Harada, Hideyuki Fujita, Tamiya Morikawa, Hidenori Shiraha, Yasushi Shiratori

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Abstract

Background & Aims: Laterally spreading tumors (LST), characterized by superficial extension along the colonic lumen, have recently been detected by colonoscopy. However, genetic and epigenetic characteristics of these tumors were scarcely reported. Methods: A total of 205 sporadic colorectal adenoma tissues (157 protruded-type, 23 granular-type LST (G-LST), 12 flat-type LST (F-LST), and 13 flat-type smaller than 1 cm) were collected. CpG island methylator phenotype (CIMP) was determined by examination of methylation status at p16, methylated in tumor (MINT) 1, 2, 12, and 31 loci. K-ras codon 12 and 13 point mutations were also examined. The relationship between macroscopic appearance and CIMP status or K-ras mutations was analyzed. Results: Among adenomas larger than 1 cm, CpG island methylation involving 2 or more loci (CIMP-high) was more likely to be observed in G-LST (14/23, 61%) than in protruded-type adenomas (18/73, 25%) (P = .002). The prevalence of K-ras mutations in G-LST (18/23, 78%) was significantly higher than that in protruded-type adenomas (18/73, 25%) (P <.0001). Moreover, the prevalence of CIMP-high and K-ras mutations in G-LST located in the proximal colon was much higher (11/13, 85%; and 12/13, 92%, respectively). In contrast, F-LST exhibited low prevalence of CIMP-high (1/12, 8%) and K-ras mutations (2/12, 16%). Conclusions: High prevalence of CIMP-high and K-ras mutations in G-LST, especially in the proximal colon, could strongly suggest that G-LST appearance is associated with a unique carcinogenic pathway.

Original languageEnglish
Pages (from-to)379-389
Number of pages11
JournalGastroenterology
Volume131
Issue number2
DOIs
Publication statusPublished - Aug 2006

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CpG Islands
Adenoma
Methylation
Phenotype
Mutation
Neoplasms
Colon
Colonoscopy
Point Mutation
Epigenomics
Codon

ASJC Scopus subject areas

  • Gastroenterology

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Laterally Spreading Type of Colorectal Adenoma Exhibits a Unique Methylation Phenotype and K-ras Mutations. / Hiraoka, Sakiko; Kato, Jun; Tatsukawa, Masashi; Harada, Keita; Fujita, Hideyuki; Morikawa, Tamiya; Shiraha, Hidenori; Shiratori, Yasushi.

In: Gastroenterology, Vol. 131, No. 2, 08.2006, p. 379-389.

Research output: Contribution to journalArticle

Hiraoka, Sakiko ; Kato, Jun ; Tatsukawa, Masashi ; Harada, Keita ; Fujita, Hideyuki ; Morikawa, Tamiya ; Shiraha, Hidenori ; Shiratori, Yasushi. / Laterally Spreading Type of Colorectal Adenoma Exhibits a Unique Methylation Phenotype and K-ras Mutations. In: Gastroenterology. 2006 ; Vol. 131, No. 2. pp. 379-389.
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abstract = "Background & Aims: Laterally spreading tumors (LST), characterized by superficial extension along the colonic lumen, have recently been detected by colonoscopy. However, genetic and epigenetic characteristics of these tumors were scarcely reported. Methods: A total of 205 sporadic colorectal adenoma tissues (157 protruded-type, 23 granular-type LST (G-LST), 12 flat-type LST (F-LST), and 13 flat-type smaller than 1 cm) were collected. CpG island methylator phenotype (CIMP) was determined by examination of methylation status at p16, methylated in tumor (MINT) 1, 2, 12, and 31 loci. K-ras codon 12 and 13 point mutations were also examined. The relationship between macroscopic appearance and CIMP status or K-ras mutations was analyzed. Results: Among adenomas larger than 1 cm, CpG island methylation involving 2 or more loci (CIMP-high) was more likely to be observed in G-LST (14/23, 61{\%}) than in protruded-type adenomas (18/73, 25{\%}) (P = .002). The prevalence of K-ras mutations in G-LST (18/23, 78{\%}) was significantly higher than that in protruded-type adenomas (18/73, 25{\%}) (P <.0001). Moreover, the prevalence of CIMP-high and K-ras mutations in G-LST located in the proximal colon was much higher (11/13, 85{\%}; and 12/13, 92{\%}, respectively). In contrast, F-LST exhibited low prevalence of CIMP-high (1/12, 8{\%}) and K-ras mutations (2/12, 16{\%}). Conclusions: High prevalence of CIMP-high and K-ras mutations in G-LST, especially in the proximal colon, could strongly suggest that G-LST appearance is associated with a unique carcinogenic pathway.",
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T1 - Laterally Spreading Type of Colorectal Adenoma Exhibits a Unique Methylation Phenotype and K-ras Mutations

AU - Hiraoka, Sakiko

AU - Kato, Jun

AU - Tatsukawa, Masashi

AU - Harada, Keita

AU - Fujita, Hideyuki

AU - Morikawa, Tamiya

AU - Shiraha, Hidenori

AU - Shiratori, Yasushi

PY - 2006/8

Y1 - 2006/8

N2 - Background & Aims: Laterally spreading tumors (LST), characterized by superficial extension along the colonic lumen, have recently been detected by colonoscopy. However, genetic and epigenetic characteristics of these tumors were scarcely reported. Methods: A total of 205 sporadic colorectal adenoma tissues (157 protruded-type, 23 granular-type LST (G-LST), 12 flat-type LST (F-LST), and 13 flat-type smaller than 1 cm) were collected. CpG island methylator phenotype (CIMP) was determined by examination of methylation status at p16, methylated in tumor (MINT) 1, 2, 12, and 31 loci. K-ras codon 12 and 13 point mutations were also examined. The relationship between macroscopic appearance and CIMP status or K-ras mutations was analyzed. Results: Among adenomas larger than 1 cm, CpG island methylation involving 2 or more loci (CIMP-high) was more likely to be observed in G-LST (14/23, 61%) than in protruded-type adenomas (18/73, 25%) (P = .002). The prevalence of K-ras mutations in G-LST (18/23, 78%) was significantly higher than that in protruded-type adenomas (18/73, 25%) (P <.0001). Moreover, the prevalence of CIMP-high and K-ras mutations in G-LST located in the proximal colon was much higher (11/13, 85%; and 12/13, 92%, respectively). In contrast, F-LST exhibited low prevalence of CIMP-high (1/12, 8%) and K-ras mutations (2/12, 16%). Conclusions: High prevalence of CIMP-high and K-ras mutations in G-LST, especially in the proximal colon, could strongly suggest that G-LST appearance is associated with a unique carcinogenic pathway.

AB - Background & Aims: Laterally spreading tumors (LST), characterized by superficial extension along the colonic lumen, have recently been detected by colonoscopy. However, genetic and epigenetic characteristics of these tumors were scarcely reported. Methods: A total of 205 sporadic colorectal adenoma tissues (157 protruded-type, 23 granular-type LST (G-LST), 12 flat-type LST (F-LST), and 13 flat-type smaller than 1 cm) were collected. CpG island methylator phenotype (CIMP) was determined by examination of methylation status at p16, methylated in tumor (MINT) 1, 2, 12, and 31 loci. K-ras codon 12 and 13 point mutations were also examined. The relationship between macroscopic appearance and CIMP status or K-ras mutations was analyzed. Results: Among adenomas larger than 1 cm, CpG island methylation involving 2 or more loci (CIMP-high) was more likely to be observed in G-LST (14/23, 61%) than in protruded-type adenomas (18/73, 25%) (P = .002). The prevalence of K-ras mutations in G-LST (18/23, 78%) was significantly higher than that in protruded-type adenomas (18/73, 25%) (P <.0001). Moreover, the prevalence of CIMP-high and K-ras mutations in G-LST located in the proximal colon was much higher (11/13, 85%; and 12/13, 92%, respectively). In contrast, F-LST exhibited low prevalence of CIMP-high (1/12, 8%) and K-ras mutations (2/12, 16%). Conclusions: High prevalence of CIMP-high and K-ras mutations in G-LST, especially in the proximal colon, could strongly suggest that G-LST appearance is associated with a unique carcinogenic pathway.

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